The better understanding of immunopathogenic pathways involved in the onset of autoimmune diseases, chronic inflammations or other immune-mediated diseases, have allowed to identify the key rote played in T-cell mediated autoimmune diseases by cytokines such as TNF-alpha, TNF-beta, IL-1beta, IL-12, IL-18 and IFN-gamma. In particular, the experimental evidences anticipating a key pathogenetic role of TNF-alpha in the pathogenesis of rheumatoid arthritis have been successfully translated to the clinical stage as specific inhibitors, namely a neutralizing monoclonal antibody [Infliximab, Humana] and a TNF receptor fusion protein, [Embrel] are currently approved for the treatment of RA patients.
Double blind clinical studies have proven that the neutralization of TNF can completely abrogate the early stage of inflammation. The specific inhibitors of TNF-alpha, in contrast to acetylsalicylic acid that subsides the inflammation, can prevent the inflammation. At first, the treatment was administered to patients with advanced disease. Upon the great beneficial success of the medication, physicians began to treat patients at an early stage of the disease. Treatment with the anti-TNF alpha drug is now utilized in other autoimmune diseases, including Crohn's disease and psoriasis. However, the production of the specific TNF-inhibitors is complex and expensive. Moreover, anti-TNF inhibitors can be only given parenterally and their chronic use may involve a greater risk of developing tuberculosis.
The demonstration of the beneficial effects of specific TNF-inhibitors in rheumatoid arthritis, Crohn's disease and psoriasis has generated efforts to discover orally available small compounds that inhibit the synthesis and/or the action of endogenous TNF and possibly other cytokines that include IFN-gamma, IL-1, IL-12, IL-18 or other cytokines.
Autoimmune diseases are immunomediated diseases that can be defined according to the organ that is attacked, according the attacking mechanism, is mediated by autoantibody or T-cells, and the development of chronic inflammation processes often mediated by cytokines. Increasing evidences suggests an important pathogenic contribution of autoimmune phenomena to atherosclerosis, psychiatric disease schizophrenia, epilepsy, baldness, peptic ulcer disease, and others.
Autoimmune diseases can affect every organ or tissue. There are autoimmune diseases that affect the nervous system, for example, multiple sclerosis. This severe disease damages the brain and causes paralysis. Other autoimmune diseases that affect the nervous system are myasthenia gravis and Guillain-Barré syndrome. Myasthenia gravis is a disease characterized by extreme muscle weakness in which the receptor that transmits electric impulse from the nerve to the muscle is destroyed. Without the transmission, there is no muscle contraction and therefore muscle weakness develops. Guillain-Barré syndrome may develop after an infection or vaccination.
There are autoimmune diseases that affect the joints, such as lupus and rheumatoid arthritis that causes deformities to the Joints. Finally, there are autoimmune diseases that damage the heart, kidneys, and lungs.